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The roles for biliary epithelial cells as antigen presenting cells or target cells in primary biliary cirrhosis

Research Project

Project/Area Number 17590657
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKYUSHU UNIVERCIT

Principal Investigator

SHIMODA Shinji  Kyushu University, Medicine and Biosystemic Science, Research Associate, 大学院医学研究院, 助手 (30279319)

Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsprimary biliary cirrhosis / biliary epithelial cells / toll-like receptor / antigen presenting cells / target cells / chemokine / T細胞クローン / 胆管上皮細胞株
Research Abstract

Biliary epithelial cells-(BEC) which established from disease liver in liver transplantation from.Primary biliary cirrhosis expressed CD40 and Toll-like receptor (TLR)2,3 and 4. BEC were examined whether they have roles as antigen presenting cells. Auto antigen pyruvate dehydrogenase complex E2 component (PDC-E2) 163-176 peptide was pulsed to BEC, and PDC-E2 163-176 reactive T cell clones (TCC) were co-coltured with the peptide profsed BEC, an TCC profiferation assay were performed. In some cases, BEC were pre-incubated with IFN-γ, CD40 ligand, TLR2,3,or 4 ligand. In all cases BEC could not proliferate TCC. BEC could not express co-stimulation molecules, CD80 or CD86 even after stimulated with IFN-γ, CD40 ligand, TLR2,3,or 4 ligand.
Next BEC were examined whether sensitivity as target cells are increased after stimulated with IFN-y, CD40 ligand, TLR2,3,or 4 ligand. BEC have roles as target cells after stimulated with IFN-y, on the other hand BEC did not have roles as target cells with other stimulation.
Finally chemokine CXCL8,CCL2,CXCL9,CXCL10,CX3CL1 and CXCL16 production from BEC were examined with or without the stimulation of IFN-γ, TLR2,3,or 4 ligand. BEC produced CXCL8 and CCL2 spontaneously. CXCL10,CX3CL1 and CXCL1G were produced after the stimulation with TLR3 ligand. IFN-γ increased the production of such chemokines.
In conclusion, BEC were clarified that they do not have roles as antigen presenting cells, that IFN-g stimulation turn BEC as target cells but other stimulation did not affect BEC as target. cells, and that BEC produce chemokines spontaneously or uniquely with TLR3 ligand.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (19 results)

All 2006 2005

All Journal Article (19 results)

  • [Journal Article] Adult T-cell leukemia development from a human T-cell leukemia virus type I carrier after a living-donor liver transplantation.2006

    • Author(s)
      Kawano N, Shimoda K, Ishikawa F, Taketomi A, Yoshizumi T, Shimoda S, Yoshida S, Uozumi K, Suzuki S, Maehara Y, Harada M
    • Journal Title

      Transplantation 27;82(6)

      Pages: 840-843

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory2006

    • Author(s)
      Shimoda S, Ishikawa F, Kamihira T, Komori A, Niiro H, Baba E, Harada K, Isse K, Nakanuma Y, Ishibashi H, Gershwin ME, Harada M
    • Journal Title

      Gastroenterology 131(2)

      Pages: 606-618

    • NAID

      10019797097

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Human intrahcpatic biliary cpithclial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways2006

    • Author(s)
      Yokoyama T, Komori A, Nakamura M, Takii Y, Kamihira T, Shimoda S, Mori T, Fujiwara S, Koyabu M, Taniguchi K, Fujioka H, Migita K, Yatsuhashi H, Ishibashi H
    • Journal Title

      Liver Int. 26(4)

      Pages: 467-476

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Purified human hematopoietic stem cells contribute to the generation of cardiomyocytes through cell fusion2006

    • Author(s)
      Ishikawa F, Shimazu H, Shultz LD, Fukata M, Nakamura R, Lyons B, Shimoda K, Shimoda S, Kanemaru T, Nakamura K, Ito H, Kaji Y, Perry AC, Harada M
    • Journal Title

      FASEB J. 20(7)

      Pages: 950-952

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Liver-targeted and peripheral blood alterations of regulatory T cells in primary biliary cirrhosis.2006

    • Author(s)
      Lan RY, Cheng C, Lian ZX, Tsuneyama K, Yang GX, Moritoki Y, Chuang YH, Nakamura T, Saito S, Shimoda S, Tanaka A, Bowlus CL, Takano Y, Ansari AA, Coppel RL, Gershwin M
    • Journal Title

      Hepatology 43(4)

      Pages: 729-737

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis2006

    • Author(s)
      Nakamura M, Takii Y, Ito M, Komori A, Yokoyama T, Shimizu-Yoshida Y, Koyabu M, Matsuyama M, Mori T, Kamihira T, Daikoku M, Migita K, Yatsuhashi H, Nozaki N, Shimoda S, Ishibashi H
    • Journal Title

      J Autoimmun. 26(2)

      Pages: 138-145

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory2006

    • Author(s)
      Shimoda S, Ishikawa F, Kamihira T, Komori A, Niiro H, Baba E, Harada K, Isse K, Nakanuma Y, Ishibashi H, Gershwin ME, Harada M.
    • Journal Title

      Gastroenterology 26(4)

      Pages: 467-76

    • NAID

      10019797097

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adult T-cell leukemia development from a human T-cell leukemia vinjs type l carrier after a living-donor liver transplantation.2006

    • Author(s)
      Kawano N, Shimoda K, Ishikawa F, Taketomi A, Yoshizumi T, Shimoda S, Yoshida S, Uozumi K, Suzuki S, Maehara Y, Harada M.
    • Journal Title

      Transplantation 27;82(6)

      Pages: 840-3

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Autoreactive T-cell responses in primary biliary cirrhosis are proinflammatory whereas those of controls are regulatory2006

    • Author(s)
      Shimoda S, Ishikawa F, Kamihira T, Komori A, Niiro H, Baba E, Harada K, Isse K, Nakanuraa Y, Ishibashi H, Gershwin ME, Harada M
    • Journal Title

      Gastroenterology 131(2)

      Pages: 606-18

    • NAID

      10019797097

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Human intrahepatic biliary epithelial cells function in innate immunity by producing IL-6 and IL-8 via the TLR4-NF-kappaB and -MAPK signaling pathways2006

    • Author(s)
      Yokoyama T, Komori A, Nakamura M, Takii Y, Kamihira T, Shimoda S, Mori T, Fujiwara S, Koyabu M, Taniguchi K, Fujioka H, Migita K, Yatsuhashi H, Ishibashi H
    • Journal Title

      Liver Int. 26(4)

      Pages: 467-76

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Altered monocyte responses to defined TLR ligands in patients with primary biliary cirrhosis.2005

    • Author(s)
      Mao TK et al.
    • Journal Title

      Hepatology. 42(4)

      Pages: 802-808

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The immune response to mitochondrial autoantigens.2005

    • Author(s)
      Ishibashi H et al.
    • Journal Title

      Semin Liver Dis. 25(3)

      Pages: 337-346

    • Related Report
      2005 Annual Research Report
  • [Journal Article] T cell immunity in autoimmune hepatitis.2005

    • Author(s)
      Ichiki Y et al.
    • Journal Title

      Autoimmun Rev. 4(5)

      Pages: 315-321

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Th1 cytokine-induced downregulation of PPARgamma in human biliary cells relates to cholangitis in primary biliary cirrhosis.2005

    • Author(s)
      Harada K et al.
    • Journal Title

      Hepatology. 41(6)

      Pages: 1329-1338

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Mitochondrial antigens as targets of cellular and humoral auto-immunity in primary biliary cirrhosis.2005

    • Author(s)
      Ichiki Y et al.
    • Journal Title

      Clin Rev Allergy Immunol. 28(2)

      Pages: 83-91

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts.2005

    • Author(s)
      Isse K et al.
    • Journal Title

      Hepatology. 41(3)

      Pages: 506-516

    • Related Report
      2005 Annual Research Report
  • [Journal Article] T cell immunity in hepatitis B and hepatitis C virus infection : implications for autoimmunity.2005

    • Author(s)
      Ichiki Y et al.
    • Journal Title

      Autoimmun Rev. 4(2)

      Pages: 82-95

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis.2005

    • Author(s)
      Nakamura M et al.
    • Journal Title

      J Hepatol. 42(3)

      Pages: 386-392

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Biliary epithelial cells regulate autoreactive T cells : implications for biliary-specific diseases.2005

    • Author(s)
      Kamihira T et al.
    • Journal Title

      Hepatology. 41(1)

      Pages: 151-159

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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